Inhibition of miR-205 Impairs the Wound-Healing Process in Human Corneal Epithelial Cells by Targeting KIR4.1 (KCNJ10)

Lin, Dao‐Hong; Halilovic, Adna; Yue, Peng; Bellner, Lars; Wang, Kemeng; Wang, Lijun; Zhang, Chengbiao

doi:10.1167/iovs.12-11577

Cited by 43 publications

(40 citation statements)

References 47 publications

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“…We show here that miR-5096 overexpression is in part responsible from this down regulation, thereby contributing to the aberrant growth of these glial derived tumor cells [8]. Such a regulation is reminiscent of what is observed in human corneal cells in which miR-205 stimulates wound healing by targeting the KCNJ10 gene [39]. More generally, the expression of membrane ion channels is frequently modulated by microRNAs, e.g.…”

Section: Discussionmentioning

confidence: 80%

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Modulation of the inwardly rectifying potassium channel Kir4.1 by the pro-invasive miR-5096 in glioblastoma cells

et al. 2017

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Inwardly rectifying potassium channels (Kir), and especially the barium-sensitive Kir4.1 encoded by KCNJ10, are key regulators of glial functions. A lower expression or mislocation of Kir4.1 is detected in human brain tumors. MicroRNAs participate in the regulation of ionic channels and associated neurologic disorders. Here, we analyze effects of miR-5096 on the Kir4.1 expression and function in two glioblastoma cell lines, U87 and U251. Using whole-cell patch-clamp and western-blot analysis, we show that cell loading with miR-5096 decreases the Kir4.1 protein level and associated K+ current. Cell treatment with barium, a Kir4.1 blocker, or cell loading of miR-5096 both increase the outgrowth of filopodia in glioma cells, as observed by time-lapse microscopy. Knocking-down Kir4.1 expression by siRNA transfection similarly increased both filopodia formation and invasiveness of glioma cells as observed in Boyden chamber assay. MiR-5096 also promotes the release of extracellular vesicles by which it increases its own transfer to surrounding cells, in a Kir4.1-dependent manner in U251 but not in U87. Altogether, our results validate Kir4.1 as a miR-5096 target to promote invasion of glioblastoma cells. Our data highlight the complexity of microRNA effects and the role of K+ channels in cancer.

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Section: Discussionmentioning

confidence: 80%

“…Although other channel proteins could be regulated by miR-5096 [49], and other microRNAs could also influence the expression and function of these channels [39–41], the use of K + channel openers appears as a potential therapeutic tool for neurologic disorders including glioblastomas.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the inwardly rectifying potassium channel Kir4.1 by the pro-invasive miR-5096 in glioblastoma cells

et al. 2017

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“…These play an important role in regulating a range of physiological and pathological processes, including cell proliferation, migration and differentiation and stem cell maintenance. Although some studies have addressed the function and role of miRNAs in the corneal epithelium (Lee et al, 2011;Lin et al, 2013;ShalomFeuerstein et al, 2012;Yu et al, 2008), little is yet known about the molecular mechanism of miRNAs in corneal homeostasis. To better understand the subject, we performed miRNA profiling of holoclone-type corneal epithelial stem cells.…”

Section: Mirna Profiling Of Holoclone-type Stem Cellsmentioning

confidence: 99%

Ocular surface reconstruction using stem cell and tissue engineering

Nakamura

Inatomi

Sotozono

et al. 2016

Progress in Retinal and Eye Research

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“…Recently, several studies have implicated miRNA functions in the regulation of cornea homeostasis. MiRNAs including miR-205 [3, 4], miR-204 [5] and miR-424 [6] have been associated with corneal wound healing. Moreover, the cornea is an ideal organ for miRNA therapy due to its ease of access and angiogenic privilege.…”

Section: Introductionmentioning

confidence: 99%

Subconjunctival injection of antagomir-21 alleviates corneal neovascularization in a mouse model of alkali-burned cornea

Zhang

et al. 2016

Oncotarget

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Corneal neovascularization may result in loss of corneal transparency and blindness. However, developing successful and inexpensive medical treatments for corneal neovascularization remains an unresolved issue. Recently, several studies have implicated miRNA functions in the regulation of cornea homeostasis. This study aimed to identify the miRNA expression profile in the neovascularized cornea after an alkali burn and to investigate the related underlying mechanisms. Here, alkali-burned corneas and matched normal tissues were pooled to perform miRNA sequencing. MiR-21 in alkali-burned cornea showed the greatest increment of abundance at 4 and 7 d after injury compared to the healthy cornea. The miR-21 expression was positively correlated with both the mRNA and protein level of key angiogenic factors including vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor-1α (HIF-1α). At 2 and 8 d after alkali burn, the mice received subconjunctival injections of antagomir-21 (1 or 5 nmol per injection). The injection of antagomir-21 (5 nmol) inactivated miR-21 and attenuated neovascularization progression by inhibiting the expression of VEGF-A and HIF-1α. Western blot analysis of the corneas demonstrated that antagomir-21 restored Sprouty 2/4 expression and silenced p-ERK activation. Therefore, these data reveal that antagomir-21 ameliorates the progression of corneal neovascularization likely via Sprouty 2/4-mediated inactivation of p-ERK. Delivery of antagomir-21 might be a potential therapeutic approach to prevent or treat visual loss caused by corneal neovascularization.

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Inhibition of miR-205 Impairs the Wound-Healing Process in Human Corneal Epithelial Cells by Targeting KIR4.1 (KCNJ10)

Cited by 43 publications

References 47 publications

Modulation of the inwardly rectifying potassium channel Kir4.1 by the pro-invasive miR-5096 in glioblastoma cells

Modulation of the inwardly rectifying potassium channel Kir4.1 by the pro-invasive miR-5096 in glioblastoma cells

Ocular surface reconstruction using stem cell and tissue engineering

Subconjunctival injection of antagomir-21 alleviates corneal neovascularization in a mouse model of alkali-burned cornea

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